Carbon-14 Lirafugratinib human mass balance study

13 evidence topics · 2 sources

Objective

Purpose of the study

“To determine the mass balance and routes and rates of excretion for lirafugratinib after a single oral dose of [14C]-lirafugratinib.” (opens the source at this quote in a new tab)
“To perform metabolite profiling and structural identification from plasma, urine, and fecal samples.” (opens the source at this quote in a new tab)

Location and study date

Study site, country, and conduct dates

No evidence found.

Study design

Design

“This was a single center, single period, non-randomized, single dose, open label study in healthy male participants to assess the mass balance recovery, pharmacokinetics (PK), metabolite profile, metabolite identification, safety, and tolerability of lirafugratinib.” (opens the source at this quote in a new tab)

Eligibility criteria

Population studied

“6 healthy, non-smoker, Caucasian male volunteers” (opens the source at this quote in a new tab)

Full inclusion and exclusion criteria

No evidence found.

Treatment

Dose, formulation, and fasting conditions

“A single [14C]-lirafugratinib 70 mg oral dose (not more than 4.8 MBq 14C) was administered in a fasted condition to 6 healthy, non-smoker, Caucasian male volunteers [median age of 39 (range: 32-50) years old; median BMI 29.1 kg/m2]. Participants received 240 mL water immediately after dosing and remained fasted until 4 h post-dose.” (opens the source at this quote in a new tab)

Study outcomes

Rationale for using total radioactivity recovery as the primary endpoint

Sampling and bioanalytical methods

“Blood, urine, and fecal samples were collected at multiple timepoints for PK evaluation until 312 hours post-dose. Total radioactivity (TR) concentrations in plasma, whole blood, urine, and feces were determined using liquid scintillation counting.” (opens the source at this quote in a new tab)

Statistical analysis description

Number of participants (Planned and analyzed)

Participants dosed

“A single [14C]-lirafugratinib 70 mg oral dose (not more than 4.8 MBq 14C) was administered in a fasted condition to 6 healthy, non-smoker, Caucasian male volunteers” (opens the source at this quote in a new tab)

Description of analysis sets

No evidence found.

Results

Participant disposition

Withdrawals

“There were no severe, serious or life-threatening TEAEs, or TEAEs leading to subject withdrawal.” (opens the source at this quote in a new tab)

Baseline characteristics

Age and body mass index

“[median age of 39 (range: 32-50) years old; median BMI 29.1 kg/m2]” (opens the source at this quote in a new tab)

Efficacy results

Absorption and distribution

“Lirafugratinib was absorbed with a median time to peak drug concentration of 3.0 hours.” (opens the source at this quote in a new tab)
“The geometric mean apparent terminal half-life for total radioactivity (17.4 hours) was similar to that estimated for lirafugratinib in plasma (14.9 hours), indicating that lirafugratinib was the most abundant plasma component.” (opens the source at this quote in a new tab)

Recovery and routes of excretion

“Approximately 87% of [14C]-lirafugratinib was recovered in excreta over the 312-hour sampling period, of which, 79.5% was excreted via feces and 7.8% via urine. Only 4% of the fecal recovery occurred within the first 48 hours post-dose, with the remainder excreted between 48 hours and 312 hours.” (opens the source at this quote in a new tab)

Circulating components and metabolites

“Unchanged lirafugratinib was identified as the predominant component in plasma, accounting for 89% of circulating TR based on AUC0-inf. No metabolites represented ≥ 10% of circulating TR (Table 3).” (opens the source at this quote in a new tab)
“In feces, 23.2% of the administered dose was recovered as unchanged lirafugratinib.” (opens the source at this quote in a new tab)
“The main metabolites in feces were dihydroxy lirafugratinib, amide hydrolyzed and N-acetylated lirafugratinib, and monohydroxy lirafugratinib.” (opens the source at this quote in a new tab)

Health-related quality of life and patient-reported outcomes

Not applicable.

Safety results

Treatment-emergent adverse events after a single dose

“Four participants (66.7%) experienced one treatment emergent adverse event (TEAE) each; all were mild and assessed as unrelated to lirafugratinib.” (opens the source at this quote in a new tab)

Study limitations

Summary

The mass balance study dosed 6 healthy male volunteers, all Caucasian, with a single 70 mg dose of [14C]-lirafugratinib in the fasted state, and is reported only in a congress poster without a registry record, site, or conduct dates. It characterizes elimination (approximately 87% of the dose recovered over 312 hours, 79.5% in feces and 7.8% in urine) and shows that unchanged drug accounted for 89% of circulating radioactivity, but it does not assess multiple dosing, women, food effect, hepatic or renal impairment, or drug interactions. The prescribing information reports no clinically significant difference in lirafugratinib pharmacokinetics after a high-fat, high-calorie meal, with CLcr 30-89 mL/min, or with mild (Child-Pugh Class A) to moderate (Child-Pugh Class B) hepatic impairment, and states that the effect of severe renal impairment (CLcr < 30 mL/min) and severe (Child-Pugh Class C) hepatic impairment is unknown; no published dedicated food-effect, hepatic impairment, or renal impairment study of lirafugratinib was located.